Discovery of structurally novel and potentially very important cancer drugs from animal, plant and microorganism sources will continue to form the sharply focused objective of the renewal Outstanding Investigator Grant (OIG) research for the National Cancer Institute (NCI). To provide the best candidates for eventual clinical trial among the current outstanding marine animal and plant anticancer substances we have discovered in collaboration with the spongistatins, dolastatins, halistatins and cephalostatins, additional emphasis will be placed on obtaining new members of these series and elucidating their structures while further advancing research knowledge necessary to the expanding clinical trials of bryostatin 1. Vigorous parallel research will continue to be strongly focused on the isolation, characterization and structural determination of new and potentially useful anticancer drugs from marine animals, plants and microorganisms. The OIG program would be used to isolate and characterize such new anticancer drugs from confirmed active extracts of marine invertebrates and vertebrates, marine and terrestrial plants, and marine microorganisms. The principal focus would be upon marine animal and plant species yielding extracts with an outstanding level of confirmed activity in the NCI's human cancer cell systems, murine xenografts and where appropriate, new microorganism and biochemical type preselection methods. Only those species that give maximum promise of yielding new drugs with potential clinical activity will be pursued with OIG funds. Other such leads of a lesser priority will be pursued with any other financial support that might be available. Because of 36 years devoted exclusively to constructing the foundation for this anticancer drug discovery research, a good number of exceedingly promising animal, microorganism and plant species have already been uncovered and will be used along with newly developed leads to maintain a very productive output of potentially useful antineoplastic substances of unique structure. As in the past the renewal OIG program will greatly assist the DCT-NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the overall renewal OIG program will be sharply focused on the discovery and very rapid development of new anticancer drugs for the National Cancer Institute's programs directed at improving human cancer treatments.